Methamphetamine (MA) abusers have cognitive deficits that may interfere with treatment and sustain drug use. We aim to delineate abnormalities in brain circuits that underlie these cognitive deficits by using functional magnetic resonance imaging (fMRI) to compare the anatomical substrates mediating cognitive control in MA abusers and demographically matched control subjects. We will pair tests of selective attention and working memory with fMRI, using signal intensity changes to index hemodynamic changes coupled with functional activity. Testing will be done at 4-7 da and 4-5 wk of abstinence, including the times when MA abusers are most likely to seek treatment. The Stroop and N-Back tasks will be used for cognitive activation. With data from a cognitive battery, thej'MRI findings will help define the cognitive resources available to abstinent MA abusers. Such knowledge can inform the design and implementation of appropriate treatments. From prior data, we predict that: the Stroop Task will activate anterior cingulate (ACC), dorsolateral prefrontal (DLPFC) and frontal polar cortices; the Stroop effect will relate positively to change in signal intensity; MA abusers will show less activation and react more slowly than controls; activation patterns will differ between groups. As Stroop performance improves in abstinent MA abusers (B.2.2.5), we expect a reduced Stroop effect to accompany greater activation in ACC and other areas at 1 mo than 1 wk abstinence. Based on prior work (B.3.2), we predict that: the N-Back Task will activate DLPFC and parietal cortex; activation will increase non-linearly with cognitive load. As prior work indicates that MA abusers have impaired working memory, and our data (Table 4) suggest that they have performance deficits, we expect: that MA abusers will show less signal change with poorer performance vs. controls; and activation pattern will differ between groups. Recent work shows differences in working memory performance between groups at the start of abstinence, but no difference when MA abusers were abstinent for 3-mo (SL Simon unpublished). We therefore expect that abstinence will improve N-Back Task performance, increasingjMRI signal change and altering the activation pattern. We expect that changes in activation pattern with abstinence will normalize functional relationships (or strengthen new routes of activation).